Potential Application of Drosophila melanogaster as a Model Organism in COVID-19-Related Research

Nainu, Firzan; Rahmatika, Dini; Emran, Talha Bin; Harapan, Harapan

doi:10.3389/fphar.2020.588561

Cited by 16 publications

(9 citation statements)

References 36 publications

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“…The utility of Drosophila as a powerful tool in our arsenal for combating present and future epidemics caused by coronaviruses has only emerged recently ( Nainu et al, 2020 ; van de Leemput and Han, 2021 ). Studies have thus exploited Drosophila to study virus-host interactions and pathogenicity.…”

Section: Introductionmentioning

confidence: 99%

ACE and ACE2: insights from Drosophila and implications for COVID-19

Herrera

Cauchi

2021

Heliyon

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Angiotensin-converting enzyme (ACE) and its homologue ACE2 are key regulators of the renin-angiotensin system and thereby cardiovascular function through their zinc-metallopeptidase activity on vasoactive peptides. ACE2 also serves as the receptor for the cellular entry of various coronaviruses including the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is responsible for the coronavirus disease 2019 (COVID-19). The unprecedented scale of the COVID-19 pandemic has spurred the use of mammalian models to investigate the SARS-ACE2 relationship and knowledge gained from such research has accelerated development of vaccines and therapeutics. Recent studies have just started to underscore the utility of the fruit fly Drosophila melanogaster as a model system to study virus-host interactions and pathogenicity. Notably, the remarkable existence of catalytically functional ACE and ACE2 orthologues in Drosophila, discovered more than two decades ago, provides a unique opportunity for further developing this model organism to better understand COVID-19 in addition to identifying coronavirus preventative and therapeutic interventions targeting ACE2. Here, we review the studies that revealed crucial insights on the biochemistry and physiology of Ance and Acer , two out of the six Drosophila ACE family members with the greatest homology to human ACE and ACE2. We highlight shared in vivo functions outside of the renin-angiotensin system, which is not conserved in flies. Importantly, we identify knowledge gaps that can be filled by further research and outline ways that can raise Drosophila to a powerful model system to combat SARS-CoV-2 and its threatening vaccine-evading variants.

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Section: Introductionmentioning

confidence: 99%

ACE and ACE2: insights from Drosophila and implications for COVID-19

Herrera

Cauchi

2021

Heliyon

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“…With its superior flexibility for genetic modification ( Bier, 2005 ; Ugur et al., 2016 ) and high genetic similarities to other insects such as mosquitoes, sand flies, and other vector insects ( Schneider, 2000 ; Zolfaghari Emameh et al., 2015 ), D. melanogaster shall allow a genetically tractable yet robust platform to assess the role of parasites’ proteins in the vector. Indeed, this insect has been extensively used in the exploration of cellular and molecular properties of human pathogens, such as bacteria and viruses, in both in vitro and in vivo conditions ( Hughes et al., 2012 ; Nainu et al., 2020 ; Harnish et al., 2021 ). Based on such notion, it would be possible to conduct similar experiments to examine the pathological role of parasites’ proteins.…”

Section: Drosophila Melanogaster As a Model Organism To Stud...mentioning

confidence: 99%

“…Several limitations may present hurdles to the experimental applications. One of the biggest constraints is the apparent differences in the anatomical and physiological profiles between Drosophila and humans ( Panayidou et al., 2014 ; Nainu et al., 2020 ), which might prevent researchers from finding the most precise answers for their research questions. However, this discrepancy also typical for other animal models, even the vertebrate (mammalian) ones.…”

Section: Drosophila Melanogaster As a Model Organism To Stud...mentioning

confidence: 99%

Drosophila melanogaster as a Versatile Model for Studying Medically Important Insect Vector-Borne Parasites

Nainu

Salim

Emran

et al. 2022

Front. Cell. Infect. Microbiol.

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“…Even though generally underutilized in viral studies, despite its potential, the fruit fly has been successfully used to investigate the molecular and physiological aspects of human virus-induced pathogenic effects on host cells in recent years, including human immunodeficiency virus (HIV), ZIKV, dengue, West Nile, as well as VSV, Epstein-Barr, human cytomegalovirus, and SARS-CoV [ 51 – 53 ]. For example, Drosophila has been employed to investigate influenza A virus, these studies have uncovered novel insights into influenza pathogenesis [ 54 ].…”

Section: Track Record Of Using Drosophila To Study Human Virusesmentioning

confidence: 99%

Drosophila, a powerful model to study virus-host interactions and pathogenicity in the fight against SARS-CoV-2

Leemput

Han

2021

Cell Biosci

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The COVID-19 pandemic is having a tremendous impact on humanity. Although COVID-19 vaccines are showing promising results, they are not 100% effective and resistant mutant SARS-CoV-2 strains are on the rise. To successfully fight against SARS-CoV-2 and prepare for future coronavirus outbreaks, it is essential to understand SARS-CoV-2 protein functions, their host interactions, and how these processes convey pathogenicity at host tissue, organ and systemic levels. In vitro models are valuable but lack the physiological context of a whole organism. Current animal models for SARS-CoV-2 research are exclusively mammals, with the intrinsic limitations of long reproduction times, few progeny, ethical concerns and high maintenance costs. These limitations make them unsuitable for rapid functional investigations of virus proteins as well as genetic and pharmacological screens. Remarkably, 90% of the SARS-CoV-2 virus-host interacting proteins are conserved between Drosophila and humans. As a well-established model system for studying human diseases, the fruit fly offers a highly complementary alternative to current mammalian models for SARS-CoV-2 research, from investigating virus protein function to developing targeted drugs. Herein, we review Drosophila’s track record in studying human viruses and discuss the advantages and limitations of using fruit flies for SARS-CoV-2 research. We also review studies that already used Drosophila to investigate SARS-CoV-2 protein pathogenicity and their damaging effects in COVID-19 relevant tissues, as well as studies in which the fly was used as an efficient whole animal drug testing platform for targeted therapeutics against SARS-CoV-2 proteins or their host interacting pathways.

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Potential Application of Drosophila melanogaster as a Model Organism in COVID-19-Related Research

Cited by 16 publications

References 36 publications

ACE and ACE2: insights from Drosophila and implications for COVID-19

ACE and ACE2: insights from Drosophila and implications for COVID-19

Drosophila melanogaster as a Versatile Model for Studying Medically Important Insect Vector-Borne Parasites

Drosophila, a powerful model to study virus-host interactions and pathogenicity in the fight against SARS-CoV-2

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